The proposed program is directed at the development of new synthetic methods and the total synthesis of biologically active natural products. An area of particular interest involves the stereo-control of prochiral sp2 sites by an allylic oxygen substituent, and its application to the total synthesis of a wide range of multifunctional natural products and their various synthetic derivatives in significant quantities for biological testing. Specific target molecules include: polyhydroxy indolizidine alkaloids, which act as potent glycosidase inhibitors; several Dendrobatid alkaloids, which provide invaluable tools for the investigation of ion transport in many biological systems; polyene mycotoxins of the citreoviridin family, which are potent inhibitors of oxidative phosphorylation; forskolin, which has been shown to activate adenylate cyclase and display a wide range of physiological effects; the seco acid of erythronolide A, the aglycon of erythromycin A, which is undoubtedly one of the most active and important macrolide antibiotics; and prostanoids, the biogenesis of which has fascinating evolutionary implications. We hope that our synthetic studies eventually would lead to mechanistic insights helpful in designing and rationalizing new stereoselective reactions. Ongoing and planned collaborations with other laboratories include investigations: to gain an understanding of the relationship between the structures of known carcinogens (such as polycyclic aromatic hydrocarbons) and their ability to modify the DNA structure, to induce mutations and to cause cancer, to determine structure and conformation of the adducted oligomers by high field NMR, circular dichroism and other biophysical techniques; to search for azasugars of therapeutic potential as antiviral and anticancer agents and for rational design and synthesis of reversible and irreversible alkaloidal glycosidase inhibitors, which should be useful in examining biological specificity at the cell surface; to elucidate biogenesis of prostanoids such as PGA2 and clavulone, which are produced in primitive marine organisms; and to determine biosynthetic pathways of polyene pyrone mycotoxins.